Andò and Capodanno (1) concluded by meta-analysis of randomized controlled trials (RCTs) that in patients with acute coronary syndrome (ACS), transradial access (TRA) improves mortality and major adverse cardiovascular event (MACE) rates compared to transfemoral access (TFA). They also point out that during sensitivity analysis, removing the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial data causes the summary results for MACE to become nonsignificant. Similarly, mortality reduction with TRA becomes statistically and clinically significant only after data from the MATRIX trial was included. These observations suggest that their conclusion was driven predominantly by the MATRIX trial data. However, they failed to point out the major limitations of the MATRIX trial, which potentially limit the generalizability of their meta-analysis (2,3).

In the MATRIX trial, the reported MACE rates were much higher in the TFA arms than was seen in other related randomized trials (2). It also showed significantly higher rates of MACE, net adverse clinical events, and mortality in the femoral group of the high radial volume centers compared with other centers (2,4). Thus, the significant difference in the outcomes between TFA and TRA in the MATRIX trial seems to be caused by the poor outcomes in the femoral group rather than the benefits of radial access (2,4).

Furthermore, a recent meta-analysis of RCTs showed that in ACS patients undergoing percutaneous coronary intervention, TFA by radial experts, compared to nonexperts, is associated with higher MACE and mortality rates (5). It is well known that the volume of patients handled by hospitals and operators correlates with outcomes. Radial experts performing in high radial volume centers are considered to be low femoral volume access centers, and this could explain the high MACE and mortality rates in the femoral group (2). This suggests that the experience of the center and operators, rather than the access site, determines outcomes.

Therefore, all the RCTs in this field must be scrutinized as to whether they are true RCTs comparing groups only by access type. In RCTs, all intervention groups must be treated identically except for the experimental treatment, but in the RCTs used here, a majority of the procedures were performed by radial experts in high radial volume centers. High radial volume centers were low-volume centers for TFA, thus leading to higher MACE and mortality rates in the TFA arms and introducing significant bias favoring the TRA arms (5). Thus, not only is the external validity (generalizability) of these RCTs an issue, but also internal validity is a major concern. These matters need further investigation before American guidelines are changed, making TRA the default access for all patients with ACS (as recommend by those who performed this meta-analysis).

Footnotes

Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.